Capture and transfer of HIV-1 particles by mature dendritic cells converges with the exosome-dissemination pathway.
Exosomes are secreted cellular vesicles that can be internalized by dendritic cells (DCs), contributing to antigen-specific naive CD4(+) T-cell activation. Here, we demonstrate that human immunodeficiency virus type 1 (HIV-1) can exploit this exosome antigen-dissemination pathway intrinsic to mature DCs (mDCs) for mediating trans-infection of T lymphocytes. Capture of HIV-1, HIV-1 Gag-enhanced green fluorescent protein (eGFP) viral-like particles (VLPs), and exosomes by DCs was up-regulated upon maturation, resulting in localization within a CD81(+) compartment. Uptake of VLPs or exosomes could be inhibited by a challenge with either particle, suggesting that the expression of common determinant(s) on VLP or exosome surface is necessary for internalization by mDCs. Capture by mDCs was insensitive to proteolysis but blocked when virus, VLPs, or exosomes were produced from cells treated with sphingolipid biosynthesis inhibitors that modulate the lipid composition of the budding particles. Finally, VLPs and exosomes captured by mDCs were transmitted to T lymphocytes in an envelope glycoprotein-independent manner, underscoring a new potential viral dissemination pathway.
Izquierdo-Useros
Nuria
N
IrsiCaixa Foundation, Badalona, Spain.
Naranjo-Gómez
Mar
M
Archer
Jacob
J
Hatch
Steven C
SC
Erkizia
Itziar
I
Blanco
Julià
J
Borràs
Francesc E
FE
Puertas
Maria Carmen
MC
Connor
John H
JH
Fernández-Figueras
Maria Teresa
MT
Moore
Landon
L
Clotet
Bonaventura
B
Gummuluru
Suryaram
S
Martinez-Picado
Javier
J
D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000187:drug effects / Q000821:virology; D002518:Ceramides / Q000096:biosynthesis / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology; D055354:Exosomes / Q000737:chemistry / Q000502:physiology*; D037341:Fumonisins / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000032:analysis; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000821:virology; D007668:Kidney; D008563:Membrane Lipids / Q000032:analysis / Q000502:physiology; D021962:Membrane Microdomains / Q000737:chemistry / Q000502:physiology*; D011402:Pronase / Q000494:pharmacology; D060225:Tetraspanin 28; D053586:Virus Internalization; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000032:analysis
D015703:Antigens, CD; C554798:CD81 protein, human; D002518:Ceramides; D037341:Fumonisins; D008563:Membrane Lipids; D060225:Tetraspanin 28; C485184:enhanced green fluorescent protein; D054301:gag Gene Products, Human Immunodeficiency Virus; D049452:Green Fluorescent Proteins; C056933:fumonisin B1; D011402:Pronase